Evaluating the Importance of Heterogeneity of Treatment Effect: Variation in Patient Utilities Can Influence Choice of the "Optimal" Oral Anticoagulant for Atrial Fibrillation.

OBJECTIVES: To investigate heterogeneity of treatment effect (HTE) for anticoagulants in atrial fibrillation across subgroups defined by 1) clinical characteristics and 2) variation in patient utilities for benefits and harms of treatment. METHODS: We reanalyzed aggregate data from a published network meta-analysis that compared four anticoagulants for atrial fibrillation (apixaban, dabigatran, edoxaban, and rivaroxaban) as well as warfarin. Event rates for stroke/systemic embolism (SE) and major bleeding were generated for each agent across seven subgroups, and rankings were developed on the basis of clinical performance. Utilities were derived from a national catalog and then applied to generate summary measures of benefit. The choice between any two agents was examined across a range of plausible utility values, defined as the interquartile range for stroke/SE and major bleeding. RESULTS: Little HTE was apparent in clinical and utility-adjusted analyses. Dabigatran 150 mg produced the lowest rates of stroke/SE, and edoxaban 30 mg had the lowest rate of major bleeding. Greater HTE was observed when utilities were varied across a plausible utility range. For example, among patients 75 years and older, dabigatran 150 mg would be preferred over edoxaban 30 mg when mean utility estimates are used. The preferred agent, however, would change at plausible utility thresholds of 0.6 and 0.7 for major bleeding and stroke/SE, respectively. Nearly 25% of all possible comparisons would see a change in preferred treatment within the plausible utility range. CONCLUSIONS: The optimal choice of anticoagulant in atrial fibrillation differs across subgroups defined by clinical characteristics and reasonable ranges of utilities.

Thin-plate spline analysis of the short- and long-term effects of rapid maxillary expansion.

The aim of this study was to investigate the short- and long-term effects induced by rapid maxillary expansion (RME) on the shape of the maxillary and circummaxillary structures by means of thin-plate spline (TPS) analysis. The sample consisted of 42 patients who were compared with a control sample of 20 subjects. The treated subjects underwent Haas-type RME, followed by fixed appliance therapy. Postero-anterior (PA) cephalograms were analysed for each treated subject at T1 (pre-treatment), T2 (immediate post-expansion), and T3 (long-term observation), and were available at T1 and T3 for the control group (CG). The mean age at T1 was 11 years and 10 months for both groups. The mean chronological ages at T3 were 20 years, 6 months for the treated group (TG) and 17 years, 8 months for the control group. The study focused on shape changes in the maxillary, nasal, zygomatic, and orbital regions. TPS analysis revealed significant shape changes in the TG. They consisted of an upward and lateral displacement of the two halves of the naso-maxillary complex as a result of active expansion in the short-term, and normalization of maxillary shape in the transverse dimension in the long-term (the initial transverse deficiency of the maxilla in the treated group was eliminated by RME therapy both in the short- and long-term). At the end of the observation period, the nasal cavities were larger when compared with both their pre-expansion configuration and the final configuration in the controls. RME with the Haas appliance appears to be an efficient therapeutic means to induce permanent favourable changes in the shape of the naso-maxillary complex.

Long-term effects of rapid maxillary expansion: a posteroanterior cephalometric evaluation.

The aim of this study was to investigate long-term effects induced by rapid maxillary expansion (RME), followed by comprehensive orthodontic treatment, in a sample of 42 patients compared with normal growth changes in a sample of 20 subjects. Treated subjects underwent Haas-type RME with 2 turns a day (0.25 mm per turn) until the expansion screw reached 10.5 mm (about 21 days). The Haas expander was kept on the teeth as a passive retainer for an average of about 2 months. Immediately after the Haas expander was removed, fixed standard edgewise appliances were placed. Posteroanterior cephalograms were analyzed for each subject in both groups at T1 (pretreatment) and at T2 (long-term observation). The mean age at T1 was 11 years 10 months for both the treated and the control groups. The mean ages at T2 also were comparable (20 years 6 months for the treated group, and 17 years 8 months for the control group). The study included transverse measurements on dentoalveolar structures, maxillary and mandibular bony bases, and other craniofacial regions (nasal, zygomatic, orbital, and cranial). RME followed by edgewise appliance therapy appears to be an effective procedure to increase transverse facial dimensions in the long term, at both the skeletal and the dentoalveolar levels. Significant pretreatment deficiencies in maxillary width, maxillary incisor apex width, and maxillary first molar width remained corrected at a mean age of about 20 years. The initial deficiency in lateroorbital width was also eliminated.